We have found cultured embryonic muscle and nerve cells rapidly replenish the enzyme acetylcholinesterase (AChE) after it has been inhibited by organophosphates diisopropylfluorophosphate (DFP) and paraoxon. Last year we showed that the rate of recovery of the enzyme was proportional to the extent of the inhibition of activity. We have also been able to follow the movement of new enzyme and the loss of activity of existing with the electron microscope. This year we will examine how paraoxon poisoning affects protein synthesis and AChE recovery, continue our electron microscope localization of AChE and, using nerve cultures, study whether organophosphates and other agents known to affect AChE activity levels also affect choline acetyltransferase, the enzyme that makes acetylcholine. The research shows how cells recover from organophosphate poisoning and how muscle and nerve cells regulate molecules important in neuromuscular transmission. BIBLIOGRAPHIC REFERENCES: Sawyer, H.R., Golder, T.K., Nieberg, P.S. and Wilson, B.W. Ultrastructural localization of acetylcholinesterase in cultured cells. I. Embryonic muscle. H. Histochem. Cytochem. 1976, In Press. Walker, C.R. and Wilson, B.W. Regulation of acetylcholinesterase in cultured muscle by chemical agents and electrical stimulation. Neuroscience 1:191-196, 1976.